Bone marrow transfusion (BMT) holds the potential to cure many blood diseases. However, BMT recipients often develop graft-versus-host disease (GvHD), a life-threatening condition in which immune cells from the infused transplant attack the recipient's tissues. Current treatments using nonspecific immunosuppressants have limited effectiveness. Moreover, there is no clinically proven method of preventing GvHD. We have developed a therapy that can prevent GvHD. In this therapy we place a recombinant protein, mFasL, on the surface of immune cells in the graft to target these cells for destruction. It is superior to current treatments since it can prevent GvHD. Another variant of our therapy can cure existing GvHD without using nonspecific immunosuppressants. During this project we will produce more mFasL and show that it can prevent or cure GvHD in vivo. In the longer term, once in vivo efficacy is shown, we will develop and market a therapeutic biologic based on mFasL. Use of the biologic will lower mortality and morbidity associated with GvHD and allow BMT to be used much more routinely in the clinic. The long-term success of this project will expand therapeutic use of BMT to cure blood diseases and to prevent allograft and xenograft rejection. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE